Ten percent of all visual impairments in the United States are caused by uveitis, an inflammation of the inner eye. Recently, NEI investigators reported significant improvement in uveitis patients following systemic therapy with cyclosporine, a potent T-cell inhibitor. Cyclosporine's safety and efficacy in ophthalmology needs to be further defined using animal models of uveitis. Topical use of drugs reduces the danger of systemic side effects. We have recently used radioimmune assay to compare the ocular penetration of cyclosporine following topical or systemic administration in rabbits. The intraocular tissue levels following topical cyclosporine administration greatly exceeded levels produced by systemic administration. After developing a cyclosporine ophthalmic preparation which penetrated deeply into all areas of the globe in therapeutic concentrations, we predicted that intraocular disease (e.g. noninfectious anterior uveitis, posterior uveitis, traumatic uveitis, sympathetic ophthalmia, phacoanaphylaxis) would be better treated by this route than by systemic cyclosporine. To test the efficacy of topically applied cyclosporine for future use in uveitis patients we wanted a severe, nonself-limiting disease involving both the anterior and posterior uvea. We chose the experimental lens induced granulomatous endophthalmitis (ELGE) model of phacoanaphylaxis as a maximal therapeutic challenge. Initial trials indicate that topical application but not oral dosing abrogated this disease. We propose to expand this study from 6 to 64 rats to fully substantiate our findings. Our findings are unique and not predicted by the current generalized conception that cyclosporine acts only through generalized immunosuppression. They represent a major diversion from current ophthalmic research with cyclosporine. This study is the first to propose use of topical cyclosporine for intraocular disease, and is a potential prototype for considering local applications in other disorders. If successful we plan to test topical cyclosporine in the S-Antigen and intravitreal foreign protein models of uveitis; alone and in combination with conventional therapies. These studies would culminate in clinical trials of topical cyclosporine for intractable uveitis.